CurrentCareSourcePolicy N/A

Xenpozyme (olipudase alfa-rpcp) coverage

Defines prior authorization and medical necessity criteria for Xenpozyme (olipudase alfa-rpcp) for treatment of non‑CNS manifestations of acid sphingomyelinase deficiency (ASMD) under the pharmacy/medical benefit.

Policy Summary

PayerCareSource

PolicyXenpozyme (olipudase alfa-rpcp) coverage

Policy CodePolicy N/A

Change TypeRevised

Effective DateOct 1, 2024

Next Review DateN/A

Key ActionObtain prior authorization and provide documentation confirming ASMD (ASM activity <10% in leukocytes or fibroblasts or two pathogenic SMPD1 mutations) plus required baseline clinical measures.

SourceLink

POLICY UPDATE CHANGES

Removed hematology and neuro from prescriber types and simplified dosing information; removed LFT monitoring from reauthorization requirements; specified <10% enzyme activity in leukocytes or fibroblasts and clarified confirmed diagnosis vs clinical diagnosis with baseline clinical measures.

6 moinitial approval duration

1 yrreauthorization approval duration

3 mg/kgmaintenance dose

<10%diagnostic threshold

2022first approved

Coverage Criteria for Xenpozyme (olipudase alfa-rpcp)

Initial Therapy

Covered when ALL of the following are met for initial authorization

Initial Authorization for Xenpozyme: 1) Medication prescribed by or in consultation with a physician knowledgeable in the management of ASMD (e.g., endocrinologist, hepatologist, or pulmonologist); 2) Confirmed diagnosis of ASMD with documentation of at least one: ASM enzyme activity <10% of controls (in leukocytes or fibroblasts) OR genetic test showing two pathogenic SMPD1 mutations; 3) Clinical diagnosis of ASMD type A/B or type B with at least one non‑CNS manifestation and baseline measure(s): splenomegaly, hepatomegaly, decreased DLco, low platelets, or delayed growth (pediatric); 4) Member does NOT have ASMD type A or rapidly progressing neurologic abnormalities; 5) Documented assessment of ALT and AST within one month prior to initiation; 6) Dosage per prescribing information: IV infusion every 2 weeks with weight‑based escalation to maintenance 3 mg/kg (adults start 0.1 mg/kg; pediatrics start 0.03 mg/kg).

If met, approve for 6 months

Continuation Therapy

Reauthorization covered when ALL of the following are met

Reauthorization for Xenpozyme:

Policy Summary

PayerCareSource

PolicyXenpozyme (olipudase alfa-rpcp) coverage

Policy CodePolicy N/A

Change TypeRevised

Effective DateOct 1, 2024

Next Review DateN/A

SourceLink

On This Page

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Chart notes must show improvement from baseline in at least one of the following: increased % predicted DLco (improved lung function), reduction of splenomegaly, reduction of hepatomegaly, increased platelet count, or improved z‑score in children with growth delay.

If met, approve for an additional 1 year

CareSource considers treatment of conditions not listed in this document (off‑label indications) to be not medically necessary. For any indication not specified in this policy, refer to the payer Off‑Label policy for determination of coverage.

Use of Xenpozyme for patients with ASMD type A is considered not medically necessary. The agent has not been studied in ASMD type A and is not expected to cross the blood‑brain barrier or improve CNS manifestations. Additionally, therapy is not covered for conditions outside those specified in this policy; such uses should be evaluated under the Off‑Label policy.

Initial Therapy Requirements and Dosing

Initial Therapy — Xenpozyme (olipudase alfa-rpcp)

Initial authorization criteria and dosing for Xenpozyme

Initial dosing and criteria for Xenpozyme: Administer as IV infusion every 2 weeks. Adults: starting dose 0.1 mg/kg then follow dose escalation per prescribing information to recommended maintenance 3 mg/kg. Pediatrics: starting dose 0.03 mg/kg then follow dose escalation per prescribing information to recommended maintenance 3 mg/kg. Prescriber must be knowledgeable in ASMD; confirmed diagnosis required; baseline clinical measures and ALT/AST within one month required.

Initial approval for 6 months

Reauthorization / Continuation Criteria

Reauthorization

Reauthorization requires clinical improvement from baseline in at least one disease parameter.

Reauth improvement criteria: Improvement in >=1 of: % predicted DLco, spleen size (reduction of splenomegaly), liver size (reduction of hepatomegaly), platelet count (increase), or pediatric growth z‑score (improvement).

Approval for 1 year if met

Diagnostic Thresholds and Codes

ASM enzyme activity — diagnostic threshold

Diagnostic thresholdASM enzyme activity <10% of controls (measured in leukocytes or fibroblasts)

Specimen typesLeukocytes or fibroblasts

PurposeUsed to confirm ASMD diagnosis for prior authorization of Xenpozyme

Provider Actions, Documentation, and Denial Triggers

Prior Authorization

Prior Authorization Required

Xenpozyme (olipudase alfa-rpcp) is a medical benefit and requires prior authorization before coverage.

Benefit type: Medical
Prior authorization required before initiation of therapy

Note

Provider action

Providers should obtain prior authorization and ensure documentation confirming ASMD and baseline labs are submitted. Prescriptions should be written or coordinated by a clinician experienced in ASMD (e.g., endocrinologist, hepatologist, pulmonologist).

Documentation Required

Required documentation for initial authorization

For initial authorization, documentation must include confirmation of ASMD via one of the following: ASM enzyme activity <10% of controls (in leukocytes or fibroblasts) OR genetic testing showing two pathogenic SMPD1 mutations. Also include clinical evidence of non-CNS ASMD manifestations with baseline measures (e.g., splenomegaly, hepatomegaly, DLco, platelet count, growth parameters for pediatrics) and ALT/AST assessment within one month prior to initiation. Note the prescriber must be knowledgeable in ASMD management.

ASM enzyme activity <10% in leukocytes or fibroblasts
Genetic test showing two pathogenic SMPD1 mutations
Documentation of at least one non‑CNS manifestation with baseline measure(s): splenomegaly, hepatomegaly, decreased DLco, low platelets, or delayed growth (pediatrics)
ALT and AST within 1 month prior to initiation
Prescribed by or in consultation with a physician experienced in ASMD

Denial Risk

Triggers for denial

Authorization will be denied if prior authorization is not obtained or if documentation does not confirm ASMD (no ASM activity <10% AND no two pathogenic SMPD1 mutations). Other denial triggers include evidence of ASMD type A or rapidly progressive neurologic disease, or missing required baseline ALT/AST.

Lack of prior authorization
Absence of documentation confirming ASMD (neither ASM activity <10% nor two pathogenic SMPD1 mutations)
Diagnosis of ASMD type A or rapidly progressive neurologic abnormalities
Missing ALT/AST assessment within one month prior to initiation

Definitions

ASMD type A — infantile neurovisceral form

DefinitionASMD type A: infantile neurovisceral form with severe CNS involvement

Treatment noteXenpozyme has not been studied in patients with ASMD type A

Clinical implicationUse for ASMD type A is considered not medically necessary per policy due to lack of CNS benefit

Confirmed ASMD diagnosis

Confirmed diagnosis criteriaASM enzyme activity <10% in leukocytes or fibroblasts OR genetic testing showing two pathogenic SMPD1 mutations

Acceptable enzymatic evidenceDocumented ASM activity <10% of controls

Acceptable genetic evidenceGenetic test demonstrating two pathogenic SMPD1 mutations

Background

Acid sphingomyelinase deficiency (ASMD), also known as Niemann‑Pick disease (types A, A/B, and B), is a rare lysosomal storage disorder caused by deficiency of the enzyme acid sphingomyelinase (ASM). Loss of ASM activity leads to accumulation of the lipid sphingomyelin in cells and results in multisystem disease, commonly including decreased lung function, hepatosplenomegaly (enlarged liver and spleen), thrombocytopenia, and growth delay in children. Xenpozyme (olipudase alfa‑rpcp) is an enzyme replacement therapy that provides the deficient ASM enzyme and is indicated for non‑central nervous system manifestations of ASMD; it was the first FDA‑approved treatment for ASMD in 2022.

Step Therapy

Step	Requirement / Description
Step 1	No step therapy requirement specified in this policy.

Quantity Limits and Dosing

Xenpozyme (olipudase alfa-rpcp) — dosing escalation

Recommended maintenance doseMaintenance dose escalation to 3 mg/kg per prescribing information

Administration frequencyIV infusion every 2 weeks

Starting dosesAdults start 0.1 mg/kg; pediatrics start 0.03 mg/kg before escalation

Site of Care and Administration

Billing Rule

Infusion center administration every 2 weeks

Administer Xenpozyme as an intravenous infusion every two weeks; follow prescribing information and payer medical‑benefit rules to determine appropriate site of care.

IV infusion every 2 weeks per dosing regimen
Site of care determined by prescribing information and payer medical benefit rules (infusion center is the indicated setting)